Recent advances in biotechnologies have led to the discovery of new protein drugs available for the treatment of various diseases. Moreover, extensive research on cellular mechanisms of these proteins has continued to progress, and thus the treatment of diseases, which have been considered very difficult to treat, has been possible. While the value of proteins as therapeutic drugs has already been recognized for a long time, a large amount of proteins are required to obtain therapeutic effects due to short half-life and instability in vivo. Furthermore, protein-based drugs are made of peptide bonds and have ionic nature under a constant pH, and protein molecules tend to aggregate or absorb each other i.e., tend to adhere to each other. Accordingly, the protein molecules are easily denatured, and the denatured proteins lose their original functions.
In order to overcome these problems, various methods of binding proteins to biodegradable polymers through covalent bonds, adsorbing protein drugs on the surface of biodegradable polymer particles, or encapsulating protein drugs in biodegradable polymer particles have been developed.
So far, a method of preparing particles using biodegradable polymers such as poly(lactide-co-glycolide) (PLGA) or poly(lactic acid) (PLA) has been widely used as one of the methods for effective delivery of proteins. Among various biodegradable polymers, the PLGA is an US FDA-approved polymer and has been extensively utilized for medical applications including microspheres, sutures, implantable screws, pins and tissue engineering scaffolds. PLGA particles have achieved a certain degree of success for the delivery of proteins and vaccines to the immune system or to the systemic circulation. Furthermore, several PLGA-based particles loaded with therapeutic drugs are available on the market. An example of particles may include leuprolide (Lupron Depot) or triptorelin (Trelstar).
However, it has been reported that the initial release of proteins as macromolecules from hydrophobic polyester microparticles such as PLGA occurs primarily through pore diffusion in non-crystalline regions and the release rate is usually very slow. Slow release of therapeutic drugs from the PLGA microparticles may not be suitable for the treatment of acute inflammatory diseases such as acute liver failure and acute lung injury. To this end, a method of blending hydrophobic PLGA with hydrophilic polymers has been used to modify the hydration rate of the polymeric matrix. In addition, the PLGA produces acidic by-products after biodegradation, which may lower the surrounding pH and cause inflammation. Therefore, there is a great need to develop biodegradable polymer particles with excellent biocompatibility.